Case Report Cardiac Aspergilloma: A Rare Case of a Cardiac Mass Involving the Native Tricuspid Valve, Right Atrium, and Right Ventricle in an Immunocompromised Patient Christina S. Chen-Milhone , 1 Kalyan Chakravarthy Potu, 2 and Sudhir Mungee 2 1 Department of Internal Medicine and Pediatrics, University of Illinois College of Medicine at Peoria, Peoria, IL, USA 2 Department of Cardiology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA Correspondence should be addressed to Christina S. Chen-Milhone; [email protected] Received 10 November 2017; Accepted 31 December 2017; Published 29 January 2018 Academic Editor: Tayfun Sahin Copyright © 2018 Christina S. Chen-Milhone et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Aspergillus can cause devastating opportunistic infections in immunocompromised patients. Rarely does this fungus invade the heart, and when it does, survival is especially poor despite optimal medical and surgical treatment. We report a case of cardiac aspergilloma with involvement of the tricuspid valve and both the right atrium and ventricle found on a transthoracic echo- cardiogram in an immunocompromised patient after developing atrial fibrillation with rapid ventricular rate. e findings from this case suggest that early clinical suspicion is critical in early diagnosis and thus early treatment. 1. Introduction Aspergillus is a common fungus in the environment that can cause fatal diseases in humans. e Aspergillus spores are easily inhaled, and immunocompromised individuals are known to be more susceptible to its disease. Acute invasive aspergillus of the heart is particularly uncommon. Asper- gillus endocarditis accounts for 20–25% of all cases of fungal endocarditis, and fungal endocarditis only comprises <2%of all cases of endocarditis [1, 2]. Invasive aspergillus involving heart valves and chambers is even rarer with only a handful of cases reported in the literature. In this report, we present a case of cardiac aspergilloma involving the native tricuspid valve and both the right atrium and ventricle that initially presented as a cardiac mass in an immunocompromised patient. 2. Case Report A 62-year-old male presented to an outlying hospital with a one-month history of productive cough, shortness of breath, and intermittent fevers, and a syncopal episode one week before. His past medical history was significant for hypertension, prostatic adenocarcinoma with bone metas- tasis, atrial fibrillation, and bilateral pulmonary embolism. e prostatic adenocarcinoma was diagnosed 11 months before, and he developed the bilateral pulmonary embolism approximately 8 months before. He completed 40 cycles of radiation, and medications included Zytiga in conjunction with prednisone, Lupron, and Eliquis. He was a former smoker and smoked a maximum of 5 cigarettes daily for 35 years. His social history was otherwise negative for high-risk sexual behavior, intravenous (IV) drug use, recent travel, and occupational exposure. He was subsequently admitted with a diagnosis of anemia with hemoglobin of 7.1g/dL and sepsis secondary to presumed pneumonia. On admission, the patient received 4 units of packed red blood cells for anemia. e patient was also noted to have thrombocytopenia with platelet count of 48,000/mcL; thus, Eliquis was held. Chest X-ray revealed a 7.4 cm opacity in the right lung base as well as multiple right pulmonary nodules (Figure 1). A CT chest showed similar findings with the addition of extensive bone metastasis. e patient was started on vancomycin and Zosyn for sepsis while awaiting blood culture results. Infectious workup was positive for Aspergillus fumigatus IgG, Aspergillus galactomannan antigen Hindawi Case Reports in Cardiology Volume 2018, Article ID 6927436, 4 pages https://doi.org/10.1155/2018/6927436
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Case Report Cardiac Aspergilloma: A Rare Case of a Cardiac Mass
Involving the Native Tricuspid Valve, Right Atrium, and Right
Ventricle in an Immunocompromised Patient
Christina S. Chen-Milhone ,1 Kalyan Chakravarthy Potu,2 and Sudhir Mungee2
1Department of Internal Medicine and Pediatrics, University of Illinois College of Medicine at Peoria, Peoria, IL, USA 2Department of Cardiology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA
Correspondence should be addressed to Christina S. Chen-Milhone; [email protected]
Received 10 November 2017; Accepted 31 December 2017; Published 29 January 2018
Academic Editor: Tayfun Sahin
Copyright © 2018 Christina S. Chen-Milhone et al. *is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in anymedium, provided the original work is properly cited.
Aspergillus can cause devastating opportunistic infections in immunocompromised patients. Rarely does this fungus invade the heart, and when it does, survival is especially poor despite optimal medical and surgical treatment. We report a case of cardiac aspergilloma with involvement of the tricuspid valve and both the right atrium and ventricle found on a transthoracic echo- cardiogram in an immunocompromised patient after developing atrial fibrillation with rapid ventricular rate. *e findings from this case suggest that early clinical suspicion is critical in early diagnosis and thus early treatment.
1. Introduction
Aspergillus is a common fungus in the environment that can cause fatal diseases in humans. *e Aspergillus spores are easily inhaled, and immunocompromised individuals are known to be more susceptible to its disease. Acute invasive aspergillus of the heart is particularly uncommon. Asper- gillus endocarditis accounts for 20–25% of all cases of fungal endocarditis, and fungal endocarditis only comprises <2% of all cases of endocarditis [1, 2]. Invasive aspergillus involving heart valves and chambers is even rarer with only a handful of cases reported in the literature. In this report, we present a case of cardiac aspergilloma involving the native tricuspid valve and both the right atrium and ventricle that initially presented as a cardiac mass in an immunocompromised patient.
2. Case Report
A 62-year-old male presented to an outlying hospital with a one-month history of productive cough, shortness of breath, and intermittent fevers, and a syncopal episode one week before. His past medical history was significant for
hypertension, prostatic adenocarcinoma with bone metas- tasis, atrial fibrillation, and bilateral pulmonary embolism. *e prostatic adenocarcinoma was diagnosed 11 months before, and he developed the bilateral pulmonary embolism approximately 8 months before. He completed 40 cycles of radiation, and medications included Zytiga in conjunction with prednisone, Lupron, and Eliquis. He was a former smoker and smoked a maximum of 5 cigarettes daily for 35 years. His social history was otherwise negative for high-risk sexual behavior, intravenous (IV) drug use, recent travel, and occupational exposure. He was subsequently admitted with a diagnosis of anemia with hemoglobin of 7.1 g/dL and sepsis secondary to presumed pneumonia.
On admission, the patient received 4 units of packed red blood cells for anemia. *e patient was also noted to have thrombocytopenia with platelet count of 48,000/mcL; thus, Eliquis was held. Chest X-ray revealed a 7.4 cm opacity in the right lung base as well as multiple right pulmonary nodules (Figure 1). A CT chest showed similar findings with the addition of extensive bone metastasis. *e patient was started on vancomycin and Zosyn for sepsis while awaiting blood culture results. Infectious workup was positive for Aspergillus fumigatus IgG, Aspergillus galactomannan antigen
Hindawi Case Reports in Cardiology Volume 2018, Article ID 6927436, 4 pages https://doi.org/10.1155/2018/6927436
(Ag), Histoplasma Ag, Fungitell, and Blastomyces antibody (Ab). Human immunodeficiency virus (HIV), herpes sim- plex virus (HSV), and influenza A and B serologies were negative. Blood cultures were negative for viruses, bacteria, and fungi. Infectious diseases were consulted. *e patient subsequently underwent a bronchoscopy, with lavage speci- mens returning positive for Aspergillus Ag but negative for pneumocystis pneumonia, HSV, bacteria, fungus including Histoplasma, and malignant cells. *e patient was then di- agnosed with presumed subacute invasive pulmonary as- pergillus. Antibiotics were then discontinued, and the patient was discharged with voriconazole for a 6-week duration.
Two days after discharge, he was admitted for atrial fibrillation with rapid ventricular rate. A transthoracic echocardiogram (TTE) was performed and showed a highly mobile 5 cm mass involving the tricuspid valve with variable involvement of the right atrium and right ventricle (Figure 2). *e ejection fraction was preserved. Infectious diseases and oncology were then consulted. *e patient remained on voriconazole, and Zytiga was discontinued as his prostate cancer was castration sensitive, per oncology. CT surgery was consulted and performed sternotomy with resection of the mass, portions of the right atrium and ventricle, and tricuspid valve on day 2 of admission. *e excised mass was pale yellow and pink, irregularly shaped, fragmented, bulky, and approximately 3× 2×1.3 cm (Figure 3). Pathology from the mass and tricuspid valve showed necrotic debris with acute inflammation and abundant fungal hyphae (Figure 4).
Cultures obtained from tissue in the operating room were positive for Aspergillus fumigatus and negative for bacteria and viruses.
*e patient did well postoperatively. He was extubated to nasal cannula within 12 hours; however, he remained on pressor support. Voriconazole was continued. On day 4 of admission, he developed septic shock, renal failure with oliguria and acidosis, and shock liver requiring increased pressor support. He continued to deteriorate the next day requiring endotracheal intubation and ventilator support. On day 5 of admission, the patient developed ventricular tachy- cardia followed by pulseless electrical activity. Shortly there- after, he was pronounced dead.*e cause of death was invasive aspergillosis-induced septic shock with multiorgan failure.
3. Discussion
Aspergilloma of the heart is a rare disease that carries a very poor prognosis. On review of the current literature, only a small number of cases have been reported. *ese cases include an invasive aspergillus of the interventricular sep- tum in an allogenic stem cell transplant patient [3], aspergilloma involving all four chambers of the heart [4], aspergillosis presenting as a pedunculated mass with mul- tiple nodules on the left ventricular wall in an acute lym- phoblastic leukemia patient [5], a large right ventricular aspergilloma in a young man on chemotherapy for acute myelogenous leukemia [6], an incidental finding of a tri- cuspid valve aspergilloma after abdominal surgery [7], and the three cases described in the correspondence by Wiwa- nitkit and Wiwanitkit [8]. Of note, all except for one of the aforementioned cases resulted in death within days to weeks after diagnosis.
Fungal endocarditis alone, without involvement of the surrounding cardiac structure, is associated with a mortality rate of at least 50% with an average survival period of 11 days [9]. Fungal endocarditis has also recently been shown to have increasing prevalence with medical and surgical ad- vancements [1, 2]. Historically, the main risk factors for developing fungal endocarditis included previous valve sur- gery, history of prosthetic valve endocarditis, prolonged use of antibiotics, rheumatic heart disease, and IV drug use [1].
Figure 1: CXR showing multiple right pulmonary nodules.
Figure 2: Transthoracic echocardiogram showing a mass involving the tricuspid valve and both the right atrium and ventricle.
Figure 3: Right atrial and tricuspid ventricular mass.
2 Case Reports in Cardiology
Most recent studies suggest that these characteristics have changed and that fungal endocarditis now more commonly affects immunocompromised patients, patients with prosthetic valves and central venous catheters, and those on broad-spectrum antibiotics [1, 2]. Of note,Aspergillus endocarditis is mostly found on aortic or mitral prosthetic valves [10] and has a mortality rate of approximately 80% [2].
Prolonged fever, as seen in the described case, is the most common presenting feature; however, some patients may present with new or changing heart murmur, chest pain, cough, dyspnea, hemoptysis, weakness, or generalized pain. Hemorrhagic black skin lesions have been reported in As- pergillus endocarditis [11]. Such symptoms in combination with leukocytosis, anemia, and thrombocytopenia may also be suggestive of fungal septicemia. As discussed earlier, an immunocompromised state, neutropenia, recent history of long-term central venous catheter, prosthetic heart valve, steroid use, prolonged antibiotic therapy, recent prolonged hospitalization, parenteral nutrition, immunocompromised status, and IV drug use predispose patients to an invasive fungal infection.
With the diverse symptoms and risk factors, the di- agnosis of fungal endocarditis is rather challenging and can be easily delayed without a high clinical suspicion, especially given that fungal pathogens are slow growing. Diagnosis is further complicated as the majority of fungi are not detected in blood cultures. Aspergillus, in particular, is positive in 4–30% of blood cultures in cases of Aspergillus endocarditis [2, 12]. Some reviews have also suggested testing for gal- actomannan antigen, which is released when Aspergillus proliferates [1, 12]. TTE is a valuable diagnostic tool in diagnosing endocarditis and has been shown to identify 89% and 76.5% of the vegetations in native and prosthetic valves, respectively [2]. Although vegetations seen on TTE may not distinguish between bacterial versus fungal etiology, fungal vegetations are typically characterized as a large, bulky, highly mobile mass, as seen in the described case, and cause an increased risk of embolic events, more commonly af- fecting the brain. Still, many cases of fungal endocarditis are diagnosed during surgery or autopsy.
Upon diagnosing fungal invasion of the heart, a multi- disciplinary team involving cardiology, infectious diseases,
and cardiovascular surgery is necessary. Most recent reviews as well as Infectious Diseases Society of America (IDSA) guidelines favor a combined medical and early surgical intervention for treatment of Aspergillus endocarditis, pericarditis, and myocarditis. Surgical valve replacement in addition to systemic antifungal therapy was noted to be pertinent to survival due to poor prognosis and risk of relapse in patients receiving only pharmacological therapy, decreased effect of antifungal medication on fungal vege- tations, large vegetations possibly compromising cardiac function, and the risk of embolic events [1, 12]. Per IDSA, the recommended initial antifungal agents are voriconazole or liposomal amphotericin B 3–5mg/kg/day, followed by lifelong antifungal treatment postsurgical valve replacement [13]. Amphotericin B is preferred for patients with hepatic insufficiency [12]. Some have proposed using caspofungin in addition to voriconazole and amphotericin [14]; however, the use of combining antifungal therapies has not been shown to be superior to monotherapy [13]. In the described case, the patient was already on voriconazole and underwent surgical resection.
*e differential diagnosis for the cardiac mass beyond a fungal etiology includes thrombus, primary cardiac tumor, myxoma, metastatic lesion, and lymphoma. *ough the patient had new-onset atrial fibrillation, a thrombus was unlikely as he had been on apixaban for approximately 6-7 months. Prostate cancer does not typically metastasize to the heart; thus, metastasis was also unlikely. Given the patient’s immunocompromised state, being on steroids, and recent diagnosis of invasive pulmonary aspergillosis, the clinical suspicion for a fungal mass was high. Hematogenous spread of invasive pulmonary aspergillus was considered in the development of cardiac aspergilloma. *e spread of invasive pulmonary aspergillus to the heart is very rare and is as- sociated with a high mortality estimated to be as high as 80–90% [15], which is approximately the same mortality rate of having Aspergillus endocarditis alone, despite aggressive pharmacological and surgical interventions [2]. However, the hematogenous spread of invasive pulmonary aspergillus would be expected to invade the left cardium rather than the right, as seen in our patient.
In considering the described case, prior to discovering the cardiac aspergilloma, the patient was already on antifungal
(a) (b)
Figure 4: Specimen of the mass with H&E stain (a) and GMS stain highlighting fungal elements (b).
Case Reports in Cardiology 3
therapy. Furthermore, once a fungal mass was suspected, the patient underwent surgery and continued antifungal treatment as per recommendations. *e overall outcome, nonetheless, was grim.
Cardiac aspergilloma remains a rare yet deadly disease that carries a high mortality rate despite aggressive phar- macological and surgical interventions. Decreasing the mortality rate remains a challenging task, given the nature of the disease and diagnostic barriers to detecting the disease early on.While innovative molecular methods can detect the diagnosis sooner than was previously possible, clinical suspicion remains the key to diagnosing the disease. Early clinical suspicion will lead to early treatment, and earlier treatment will presumably result in decreased mortality.
Conflicts of Interest
*e authors declare that there are no conflicts of interest regarding the publication of this paper.
Acknowledgments
*e authors thank Dr. Janeen N. Buonaccorsi for assistance with providing the pathology slides for the case report and Dr. Matthew Mischler, Assistant Professor at University of Illinois College of Medicine at Peoria, for comments that greatly helped with the manuscript.
References
[1] P. Tattevin, M. Revest, A. Lefort, C. Michelet, and O. Lortholary, “Fungal endocarditis: current challenges,” International Journal of Antimicrobial Agents, vol. 44, no. 4, pp. 290–294, 2014.
[2] L. C. Pierrotti and L. M. Baddour, “Fungal endocarditis, 1995–2002,” Chest, vol. 122, no. 1, pp. 302–310, 2002.
[3] M. Paul, A. Schuster, S. T. Hussain, E. Nagel, and A. Chiribiri, “Invasive aspergillosis, extensive cardiac involvement dem- onstrated by cardiac magnetic resonance,” Circulation, vol. 126, no. 14, pp. 1780–1783, 2012.
[4] S. O. Soman, G. Vijayaraghavan, N. P. Padmaja, A. R.Warrier, and M. Unni, “Aspergilloma of the heart,” Indian Heart Journal, vol. 66, no. 2, pp. 238–240, 2014.
[5] J. Alvarez Rubiolvarez, J. Sierra Quiroga, C. Rubio Taboada, A. Fernandez Gonzalez, F. Martinon Torres, and J. Garcia- Bengochea, “Cardiac aspergillosis with pedunculated mass in the left ventricle,” Texas Heart Institute Journal, vol. 31, no. 4, pp. 439–441, 2004.
[6] H.W. Chou, M. K. Chuang, and Y. S. Chen, “Rapid recurrence of right ventricular aspergilloma,” European Journal of Cardio-)oracic Surgery, vol. 44, no. 5, p. 965, 2013.
[7] M. K. Singla, A. Shrivastava, K. C. Mukherjee, and K. Sodhi, “Potentially fatal tricuspid valve aspergilloma detected after laparoscopic abdominal surgery,” Southern African Journal of Anaesthesia and Analgesia, vol. 17, no. 3, pp. 266–268, 2011.
[8] S. Wiwanitkit and V. Wiwanitkit, “Cardiac aspergilloma,” Indian Heart Journal, vol. 67, no. 3, p. 288, 2015.
[9] M. E. Ellis, H. Al-Abdely, A. Sandridge, W. Greer, and W. Ventura, “Fungal endocarditis: evidence in the world literature 1965–1995,” Clinical Infectious Diseases, vol. 32, no. 1, pp. 50–62, 2001.
[10] A. C. Pasqualotto and D. W. Denning, “Post-operative aspergillosis,” Clinical Microbiology and Infection, vol. 12, no. 11, pp. 1060–1076, 2006.
[11] G. M. Varghese and J. D. Sobel, “Fungal endocarditis,” Current Infectious Disease Reports, vol. 10, no. 4, pp. 275–279, 2008.
[12] A. K. Pasha, J. Z. Lee, S. W. Low, H. Desai, K. S. Lee, andM. Al Mohajer, “Fungal endocarditis: update on diagnosis and management,” )e American Journal of Medicine, vol. 129, no. 10, pp. 1037–1043, 2016.
[13] T. F. Patterson, G. R. *ompson III, D. W. Denning et al., “Practice guidelines for the diagnosis and management of aspergillosis: 2016 Update by the Infectious Diseases Society of America,” Clinical Infectious Diseases, vol. 63, no. 4, pp. e1– e60, 2016.
[14] S. M. Yuan, “Fungal endocarditis,” Brazilian Journal of Cardiovascular Surgery, vol. 31, no. 3, pp. 252–255, 2016.
[15] B. Sulik-Tyszka, P. Kacprzyk, K. Madry, B. Ziarkiewicz- Wroblewska, W. Jedrzejczak, and M. Wroblewska, “Asper- gillosis of the heart and lung and review of published reports on fungal endocarditis,” Mycopathologia, vol. 181, no. 7-8, pp. 583–588, 2016.
4 Case Reports in Cardiology
Stem Cells International
Hindawi www.hindawi.com Volume 2018
The Scientific World Journal
Journal of
Hindawi www.hindawi.com Volume 2018
Volume 2018 Hindawi www.hindawi.com
Christina S. Chen-Milhone ,1 Kalyan Chakravarthy Potu,2 and Sudhir Mungee2
1Department of Internal Medicine and Pediatrics, University of Illinois College of Medicine at Peoria, Peoria, IL, USA 2Department of Cardiology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA
Correspondence should be addressed to Christina S. Chen-Milhone; [email protected]
Received 10 November 2017; Accepted 31 December 2017; Published 29 January 2018
Academic Editor: Tayfun Sahin
Copyright © 2018 Christina S. Chen-Milhone et al. *is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in anymedium, provided the original work is properly cited.
Aspergillus can cause devastating opportunistic infections in immunocompromised patients. Rarely does this fungus invade the heart, and when it does, survival is especially poor despite optimal medical and surgical treatment. We report a case of cardiac aspergilloma with involvement of the tricuspid valve and both the right atrium and ventricle found on a transthoracic echo- cardiogram in an immunocompromised patient after developing atrial fibrillation with rapid ventricular rate. *e findings from this case suggest that early clinical suspicion is critical in early diagnosis and thus early treatment.
1. Introduction
Aspergillus is a common fungus in the environment that can cause fatal diseases in humans. *e Aspergillus spores are easily inhaled, and immunocompromised individuals are known to be more susceptible to its disease. Acute invasive aspergillus of the heart is particularly uncommon. Asper- gillus endocarditis accounts for 20–25% of all cases of fungal endocarditis, and fungal endocarditis only comprises <2% of all cases of endocarditis [1, 2]. Invasive aspergillus involving heart valves and chambers is even rarer with only a handful of cases reported in the literature. In this report, we present a case of cardiac aspergilloma involving the native tricuspid valve and both the right atrium and ventricle that initially presented as a cardiac mass in an immunocompromised patient.
2. Case Report
A 62-year-old male presented to an outlying hospital with a one-month history of productive cough, shortness of breath, and intermittent fevers, and a syncopal episode one week before. His past medical history was significant for
hypertension, prostatic adenocarcinoma with bone metas- tasis, atrial fibrillation, and bilateral pulmonary embolism. *e prostatic adenocarcinoma was diagnosed 11 months before, and he developed the bilateral pulmonary embolism approximately 8 months before. He completed 40 cycles of radiation, and medications included Zytiga in conjunction with prednisone, Lupron, and Eliquis. He was a former smoker and smoked a maximum of 5 cigarettes daily for 35 years. His social history was otherwise negative for high-risk sexual behavior, intravenous (IV) drug use, recent travel, and occupational exposure. He was subsequently admitted with a diagnosis of anemia with hemoglobin of 7.1 g/dL and sepsis secondary to presumed pneumonia.
On admission, the patient received 4 units of packed red blood cells for anemia. *e patient was also noted to have thrombocytopenia with platelet count of 48,000/mcL; thus, Eliquis was held. Chest X-ray revealed a 7.4 cm opacity in the right lung base as well as multiple right pulmonary nodules (Figure 1). A CT chest showed similar findings with the addition of extensive bone metastasis. *e patient was started on vancomycin and Zosyn for sepsis while awaiting blood culture results. Infectious workup was positive for Aspergillus fumigatus IgG, Aspergillus galactomannan antigen
Hindawi Case Reports in Cardiology Volume 2018, Article ID 6927436, 4 pages https://doi.org/10.1155/2018/6927436
(Ag), Histoplasma Ag, Fungitell, and Blastomyces antibody (Ab). Human immunodeficiency virus (HIV), herpes sim- plex virus (HSV), and influenza A and B serologies were negative. Blood cultures were negative for viruses, bacteria, and fungi. Infectious diseases were consulted. *e patient subsequently underwent a bronchoscopy, with lavage speci- mens returning positive for Aspergillus Ag but negative for pneumocystis pneumonia, HSV, bacteria, fungus including Histoplasma, and malignant cells. *e patient was then di- agnosed with presumed subacute invasive pulmonary as- pergillus. Antibiotics were then discontinued, and the patient was discharged with voriconazole for a 6-week duration.
Two days after discharge, he was admitted for atrial fibrillation with rapid ventricular rate. A transthoracic echocardiogram (TTE) was performed and showed a highly mobile 5 cm mass involving the tricuspid valve with variable involvement of the right atrium and right ventricle (Figure 2). *e ejection fraction was preserved. Infectious diseases and oncology were then consulted. *e patient remained on voriconazole, and Zytiga was discontinued as his prostate cancer was castration sensitive, per oncology. CT surgery was consulted and performed sternotomy with resection of the mass, portions of the right atrium and ventricle, and tricuspid valve on day 2 of admission. *e excised mass was pale yellow and pink, irregularly shaped, fragmented, bulky, and approximately 3× 2×1.3 cm (Figure 3). Pathology from the mass and tricuspid valve showed necrotic debris with acute inflammation and abundant fungal hyphae (Figure 4).
Cultures obtained from tissue in the operating room were positive for Aspergillus fumigatus and negative for bacteria and viruses.
*e patient did well postoperatively. He was extubated to nasal cannula within 12 hours; however, he remained on pressor support. Voriconazole was continued. On day 4 of admission, he developed septic shock, renal failure with oliguria and acidosis, and shock liver requiring increased pressor support. He continued to deteriorate the next day requiring endotracheal intubation and ventilator support. On day 5 of admission, the patient developed ventricular tachy- cardia followed by pulseless electrical activity. Shortly there- after, he was pronounced dead.*e cause of death was invasive aspergillosis-induced septic shock with multiorgan failure.
3. Discussion
Aspergilloma of the heart is a rare disease that carries a very poor prognosis. On review of the current literature, only a small number of cases have been reported. *ese cases include an invasive aspergillus of the interventricular sep- tum in an allogenic stem cell transplant patient [3], aspergilloma involving all four chambers of the heart [4], aspergillosis presenting as a pedunculated mass with mul- tiple nodules on the left ventricular wall in an acute lym- phoblastic leukemia patient [5], a large right ventricular aspergilloma in a young man on chemotherapy for acute myelogenous leukemia [6], an incidental finding of a tri- cuspid valve aspergilloma after abdominal surgery [7], and the three cases described in the correspondence by Wiwa- nitkit and Wiwanitkit [8]. Of note, all except for one of the aforementioned cases resulted in death within days to weeks after diagnosis.
Fungal endocarditis alone, without involvement of the surrounding cardiac structure, is associated with a mortality rate of at least 50% with an average survival period of 11 days [9]. Fungal endocarditis has also recently been shown to have increasing prevalence with medical and surgical ad- vancements [1, 2]. Historically, the main risk factors for developing fungal endocarditis included previous valve sur- gery, history of prosthetic valve endocarditis, prolonged use of antibiotics, rheumatic heart disease, and IV drug use [1].
Figure 1: CXR showing multiple right pulmonary nodules.
Figure 2: Transthoracic echocardiogram showing a mass involving the tricuspid valve and both the right atrium and ventricle.
Figure 3: Right atrial and tricuspid ventricular mass.
2 Case Reports in Cardiology
Most recent studies suggest that these characteristics have changed and that fungal endocarditis now more commonly affects immunocompromised patients, patients with prosthetic valves and central venous catheters, and those on broad-spectrum antibiotics [1, 2]. Of note,Aspergillus endocarditis is mostly found on aortic or mitral prosthetic valves [10] and has a mortality rate of approximately 80% [2].
Prolonged fever, as seen in the described case, is the most common presenting feature; however, some patients may present with new or changing heart murmur, chest pain, cough, dyspnea, hemoptysis, weakness, or generalized pain. Hemorrhagic black skin lesions have been reported in As- pergillus endocarditis [11]. Such symptoms in combination with leukocytosis, anemia, and thrombocytopenia may also be suggestive of fungal septicemia. As discussed earlier, an immunocompromised state, neutropenia, recent history of long-term central venous catheter, prosthetic heart valve, steroid use, prolonged antibiotic therapy, recent prolonged hospitalization, parenteral nutrition, immunocompromised status, and IV drug use predispose patients to an invasive fungal infection.
With the diverse symptoms and risk factors, the di- agnosis of fungal endocarditis is rather challenging and can be easily delayed without a high clinical suspicion, especially given that fungal pathogens are slow growing. Diagnosis is further complicated as the majority of fungi are not detected in blood cultures. Aspergillus, in particular, is positive in 4–30% of blood cultures in cases of Aspergillus endocarditis [2, 12]. Some reviews have also suggested testing for gal- actomannan antigen, which is released when Aspergillus proliferates [1, 12]. TTE is a valuable diagnostic tool in diagnosing endocarditis and has been shown to identify 89% and 76.5% of the vegetations in native and prosthetic valves, respectively [2]. Although vegetations seen on TTE may not distinguish between bacterial versus fungal etiology, fungal vegetations are typically characterized as a large, bulky, highly mobile mass, as seen in the described case, and cause an increased risk of embolic events, more commonly af- fecting the brain. Still, many cases of fungal endocarditis are diagnosed during surgery or autopsy.
Upon diagnosing fungal invasion of the heart, a multi- disciplinary team involving cardiology, infectious diseases,
and cardiovascular surgery is necessary. Most recent reviews as well as Infectious Diseases Society of America (IDSA) guidelines favor a combined medical and early surgical intervention for treatment of Aspergillus endocarditis, pericarditis, and myocarditis. Surgical valve replacement in addition to systemic antifungal therapy was noted to be pertinent to survival due to poor prognosis and risk of relapse in patients receiving only pharmacological therapy, decreased effect of antifungal medication on fungal vege- tations, large vegetations possibly compromising cardiac function, and the risk of embolic events [1, 12]. Per IDSA, the recommended initial antifungal agents are voriconazole or liposomal amphotericin B 3–5mg/kg/day, followed by lifelong antifungal treatment postsurgical valve replacement [13]. Amphotericin B is preferred for patients with hepatic insufficiency [12]. Some have proposed using caspofungin in addition to voriconazole and amphotericin [14]; however, the use of combining antifungal therapies has not been shown to be superior to monotherapy [13]. In the described case, the patient was already on voriconazole and underwent surgical resection.
*e differential diagnosis for the cardiac mass beyond a fungal etiology includes thrombus, primary cardiac tumor, myxoma, metastatic lesion, and lymphoma. *ough the patient had new-onset atrial fibrillation, a thrombus was unlikely as he had been on apixaban for approximately 6-7 months. Prostate cancer does not typically metastasize to the heart; thus, metastasis was also unlikely. Given the patient’s immunocompromised state, being on steroids, and recent diagnosis of invasive pulmonary aspergillosis, the clinical suspicion for a fungal mass was high. Hematogenous spread of invasive pulmonary aspergillus was considered in the development of cardiac aspergilloma. *e spread of invasive pulmonary aspergillus to the heart is very rare and is as- sociated with a high mortality estimated to be as high as 80–90% [15], which is approximately the same mortality rate of having Aspergillus endocarditis alone, despite aggressive pharmacological and surgical interventions [2]. However, the hematogenous spread of invasive pulmonary aspergillus would be expected to invade the left cardium rather than the right, as seen in our patient.
In considering the described case, prior to discovering the cardiac aspergilloma, the patient was already on antifungal
(a) (b)
Figure 4: Specimen of the mass with H&E stain (a) and GMS stain highlighting fungal elements (b).
Case Reports in Cardiology 3
therapy. Furthermore, once a fungal mass was suspected, the patient underwent surgery and continued antifungal treatment as per recommendations. *e overall outcome, nonetheless, was grim.
Cardiac aspergilloma remains a rare yet deadly disease that carries a high mortality rate despite aggressive phar- macological and surgical interventions. Decreasing the mortality rate remains a challenging task, given the nature of the disease and diagnostic barriers to detecting the disease early on.While innovative molecular methods can detect the diagnosis sooner than was previously possible, clinical suspicion remains the key to diagnosing the disease. Early clinical suspicion will lead to early treatment, and earlier treatment will presumably result in decreased mortality.
Conflicts of Interest
*e authors declare that there are no conflicts of interest regarding the publication of this paper.
Acknowledgments
*e authors thank Dr. Janeen N. Buonaccorsi for assistance with providing the pathology slides for the case report and Dr. Matthew Mischler, Assistant Professor at University of Illinois College of Medicine at Peoria, for comments that greatly helped with the manuscript.
References
[1] P. Tattevin, M. Revest, A. Lefort, C. Michelet, and O. Lortholary, “Fungal endocarditis: current challenges,” International Journal of Antimicrobial Agents, vol. 44, no. 4, pp. 290–294, 2014.
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